19-34931927-G-T

Position:

• chr19-34931927-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_194325.3(ZNF30):​c.94G>T​(p.Asp32Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF30 NM_194325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.339

Genes affected

ZNF30 (HGNC:13090): (zinc finger protein 30) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF30 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF30	NM_194325.3	c.94G>T	p.Asp32Tyr	missense_variant	3/5	ENST00000601142.2	NP_919306.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF30	ENST00000601142.2	c.94G>T	p.Asp32Tyr	missense_variant	3/5	2	NM_194325.3	ENSP00000469954.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.94G>T (p.D32Y) alteration is located in exon 3 (coding exon 2) of the ZNF30 gene. This alteration results from a G to T substitution at nucleotide position 94, causing the aspartic acid (D) at amino acid position 32 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.13	.;.;.;.;T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.33	.;T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M;M;.;M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.9	D;D;.;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.47	P;P;.;.;D
Vest4		0.38
MutPred		0.68		Loss of disorder (P = 0.0424);Loss of disorder (P = 0.0424);Loss of disorder (P = 0.0424);Loss of disorder (P = 0.0424);Loss of disorder (P = 0.0424);
MVP		0.54
MPC		0.12
ClinPred		0.98	D
GERP RS		0.50
Varity_R		0.55
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35422831; COSMIC: COSV100340576; COSMIC: COSV100340576;